To date, various transdermal delivery systems (TDS) for the administration of amine functional drugs, such as rotigotine and many others, have been described. WO 94/07468 discloses a TDS containing rotigotine hydrochloride as active substance in a two-phase matrix, which is essentially formed by a hydrophobic polymer material as the continuous phase and a disperse hydrophilic phase contained therein and mainly containing the drug and hydrated silica. The silica is said to enhance the maximum possible loading of the TDS with the hydrophilic salt. Moreover, the formulation of WO 94/07468 usually contains additional hydrophobic solvents, permeation promoting substances, dispersing agents and, in particular, an emulsifier which is required to emulsify the aqueous solution of the active component in the lipophilic polymer phase. A TDS prepared by using such a system has been tested in healthy subjects and Parkinson's patients. However, no satisfactory drug plasma levels were achieved.
Various further TDSs have been described in WO 99/49852.
In the TDS according to WO 94/07468 and many related applications, passive diffusion membranes were used.
However, as the skin is to be seen as a very efficient barrier for most drug candidates, such type of membrane controlled systems are more or less limited in practice to transdermal delivery of active substances that reveal a very high skin permeability. Additionally, special requirements on drug release kinetics have to be met like contact delivery over several days.
An object of the present invention is to control (i.e. to canalise/manoeuvre) the transport of a drug substance towards and across the skin from a drug reservoir, thereby enhancing the flux of the drug substance across the TDS/skin interface.
A further object and aspect of the present invention is to provide a suitable composition and manufacturing methods of polymer matrices in TDS which lead to an enhanced delivery of weakly basic amines to and across the skin by                (i) preventing back diffusion of the drug portion which is ionized in the skin according to its pKa value from the skin tissue into the TDS,        (ii) offering continuous delivery of the active compound across the stratum corneum not only via the common more lipophilic route (e.g. intercellular) but also through hydrophilic pores (e.g. eccrine sweat glands).        